Research done in vitro has shown that GLP-1 is mildly insulinomimetic in both fat and muscle. We therefore initiated a study in obese, non diabetic (insulin resistant, with normal fasting blood glucose) subjects to see if GLP-1 would improve resistance to insulin. We finished the study in 12 subjects whose BMI was >30. It does appear that GLP-1 is indeed insulinomimetic (i.e. augments insulin action) in obese people. A previous report showed it to be insulinomimetic in the elderly (aging per se is accompanied by insulin resistance). It also appears to suppress formation of non-esterified fatty acids more than does insulin alone. This tells us that a GLP-1-like compound, such as GLP-1 itself or exendin-4, might not only be useful in diabetes, but also in glucose intolerance. In type 2 diabetes itself treatment options that are presently available are less than perfect. The vast majority of type 2 diabetic subjects require insulin at some point in their lives because of deteriorating beta cell function. Project Number Z01AG00214-11 LCI has shown that continuous GLP-1 treatment improves glucose tolerance and increases the rate of beta cell turnover in rodents. GLP-1, given subcutaneously to humans before each meal, does lower blood sugar. But blood sugar levels rise again before the next bolus. We are collaborating in a study involving GLP-1 administration elderly (>72 yrs old) to type 2 dm subjects, via Mini-Med-pump for 3 months, (GRC00-04-24-01). Our preliminary data show that there is no tachyphylaxis to the compound, as it is still insulinotropic even after the 3 months.